rs2978381

Positions:

• chr14-64299934-T-C
• chr14-64299934-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291712.2(ESR2):​c.-371+1434A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,962 control chromosomes in the GnomAD database, including 22,764 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (22764 hom., cov: 31)
• Consequence: ESR2 NM_001291712.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.906

Genes affected

ESR2 (HGNC:3468): (estrogen receptor 2) This gene encodes a member of the family of estrogen receptors and superfamily of nuclear receptor transcription factors. The gene product contains an N-terminal DNA binding domain and C-terminal ligand binding domain and is localized to the nucleus, cytoplasm, and mitochondria. Upon binding to 17beta-estradiol or related ligands, the encoded protein forms homo- or hetero-dimers that interact with specific DNA sequences to activate transcription. Some isoforms dominantly inhibit the activity of other estrogen receptor family members. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been fully characterized. [provided by RefSeq, Jul 2008]

ESR2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR2	NM_001291712.2	c.-371+1434A>G		intron_variant			NP_001278641.1
ESR2	NM_001291723.1	c.-90-16859A>G		intron_variant			NP_001278652.1
ESR2	XM_047431076.1	c.-90-16859A>G		intron_variant			XP_047287032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000554572.5	c.-371+1434A>G		intron_variant		1		ENSP00000450699.1
ESR2	ENST00000358599.9	c.-90-16859A>G		intron_variant		2		ENSP00000351412.5

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78721 AN: 151844 Hom.: 22729 Cov.: 31

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.514

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.519 AC: 78808 AN: 151962 Hom.: 22764 Cov.: 31 AF XY: 0.508 AC XY: 37749 AN XY: 74272

Gnomad4 AFR AF: 0.790

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.509

Alfa AF: 0.441 Hom.: 20290

Bravo AF: 0.541

Asia WGS AF: 0.413 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.96
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2978381; hg19: chr14-64766652;